Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New Perspectives of Antimicrobial Peptide-Based Therapies.
Antimicrobial Activity of Mesenchymal Stem Cells: Current Status and New Perspectives of Antimicrobial Peptide-Based Therapies.
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DOI：
10.3389/fimmu.2017.00339
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发表时间：
2017
影响因子：
7.3
通讯作者：
Khoury M
中科院分区：
文献类型：
--
作者：
Alcayaga-Miranda F;Cuenca J;Khoury M
虽然基于间充质干细胞（MSC）的治疗似乎是有希望的，但人们担心可能会出现与抗菌免疫力的不必要抑制相关的副作用，导致感染风险增加。相反，最近的数据表明，MSC通过间接和直接机制发挥强大的抗菌作用，部分由抗菌肽和蛋白质（AMP）的分泌介导。事实上，已经报道了MSC在败血症、急性呼吸窘迫综合征和囊性纤维化相关感染的临床前模型中增加细菌清除。本文综述了目前有关MSC的直接抗菌效应功能的证据，主要集中在MSC衍生的抗菌肽的作用。强调了可能调节这些AMP的表达和分泌，从而增强抗菌作用的策略。此外，评估AMP在细胞外囊泡（EV）货物中的存在的研究被强调为开发新的药物递送工具的前景机会。MSC衍生的EV的抗微生物潜力也可以通过细胞调节和/或药物负载来提高。最后，除了破译AMP的多靶点药物状态之外，改善药代动力学和递送应该协同地导致对抗由耐药菌株引起的感染的关键进展。
While mesenchymal stem cells (MSCs)-based therapy appears to be promising, there are concerns regarding possible side effects related to the unwanted suppression of antimicrobial immunity leading to an increased risk of infection. Conversely, recent data show that MSCs exert strong antimicrobial effects through indirect and direct mechanisms, partially mediated by the secretion of antimicrobial peptides and proteins (AMPs). In fact, MSCs have been reported to increase bacterial clearance in preclinical models of sepsis, acute respiratory distress syndrome, and cystic fibrosis-related infections. This article reviews the current evidence regarding the direct antimicrobial effector function of MSCs, focusing mainly on the role of MSCs-derived AMPs. The strategies that might modulate the expression and secretion of these AMPs, leading to enhanced antimicrobial effect, are highlighted. Furthermore, studies evaluating the presence of AMPs in the cargo of extracellular vesicles (EVs) are underlined as perspective opportunities to develop new drug delivery tools. The antimicrobial potential of MSCs-derived EVs can also be heightened through cell conditioning and/or drug loading. Finally, improving the pharmacokinetics and delivery, in addition to deciphering the multi-target drug status of AMPs, should synergistically lead to key advances against infections caused by drug-resistant strains.